XML Template (2009) [7.9.2009–9:27am] [1–14]
{TANDF_FPP}CMO/CMO_A_370737(NEW).3d (CMO) [First Proof]
Current Medical Research and Opinion
C213
Volume 25, Number 3 2008
efficacy comparisons, data collected after initiation of population were reported previously
15
. In the present ana-
rescue therapy were treated as missing. An analysis of cov- lysis, for the CAPT population, the baseline demographics
ariance (ANCOVA) model evaluated treatment groups and efficacy characteristics for the treatment groups were
for continuous efficacy parameters, focusing on change generally well balanced, although the combination ther-
from baseline at week 54, with baseline values and prior apy groups tended to have higher mean FPG values
oral AHA status as covariates. Missing data were handled (Table2).Overthe54-weekstudywithprogressively stric-
with the last observation-carried-forward (LOCF) method ter glycemic rescue criteria, the proportion of patients in
within the continuation phase, but not from phase A to the co-administration groups (28% [low dose] and 15%
the continuation phase. Additional efficacy analyses were [high dose]) requiring glycemic rescue therapy was lower
performedonapopulationthatconsistedofallrandomized when compared with their respective monotherapy groups
patients who had baseline and week 54 glycemic measure- (44% on metformin 500mg b.i.d., 32% on metformin
ments and did not require glycemic rescue medication 1000mg b.i.d., and 56% on sitagliptin).
during the study (week 54 completers population) for
select key endpoints: HbA
1c
, FPG and 2-hour PPG. No
Efficacy
missing data were imputed in the week 54 completers ana-
lysis. The within-group differences (least-squares [LS] The efficacy results focus on the CAPT population, which
mean changes from baseline at week 54) with 95% con- included 72% of patients treated with active therapies in
fidence intervals (CI) and sample sizes were summarized both phase A and the continuation phase (range¼59–
for the efficacy endpoints for the patients who were con- 84% across active treatment groups). The LS mean
tinuously treated with active therapy in phase A and the changes from baseline in HbA
1c
at week 54 were C01.8%,
continuation phase. No inferential testing was performed C01.4%, C01.3%, C01.0% and C00.8% for the high-dose co-
between groups in the continuation phase. administration, low-dose co-administration, metformin
Patients switched from placebo to metformin at week 1000mg b.i.d., metformin 500mg b.i.d., and sitagliptin
24 do not represent the original randomized population groups, respectively (Table 3). Continued improvement
because they included only those who did not discontinue in the HbA1c
response was noted through week 24, with
during phase A (placebo-controlled period) and who were
most groups showing a nadir in HbA
1c
near week 30
able to complete the 24-week phase A period without
(Figure 1A). Greater reductions in HbA
1c
from baseline
requiring glycemic rescue therapy. Further, because the
were observed in patients with higher baseline HbA
1c
metformin in this switch group and the continuous treat-
levels (Figure 2). The proportions of patients with an
mentintheothergroupswerenotinitiatedsimultaneously
HbA
1c
57% at week 54 were 67%, 48%, 44%, 25%, and
at randomization, the durations of the active treatment
23% for the high-dose co-administration, low-dose co-ad-
period differed between groups. Therefore, the results
ministration,metformin1000mgb.i.d.,metformin500mg
from the switch group were not included in the efficacy
b.i.d., and sitagliptin groups, respectively. Among the
analyses.
patients in the CAPT population with an HbA
1c
57%
The safety analysis was based on the 54-week results for
in the week 24 analysis, the proportions with an
the all-patients-as-treated (APaT)population, which con-
HbA
1c
57% in the week 54 analysis were 86% (n/N: 92/
sisted of all randomized patients who received at least one
107), 80% (57/71), 77% (52/68), 55% (21/38), and 68%
dose of study medication. The primary safety analysis
(23/34) for the high-dose co-administration, low-dose co-
excluded adverse experiences obtained after initiation of
administration, metformin 1000mg b.i.d., metformin
glycemic rescue therapy. In addition to the results for the
500mg b.i.d., and sitagliptin groups, respectively.
patients continuously treated with active therapy over 54
Fortheweek54completerspopulation,51%ofpatients
weeks, results for patients initially randomized to placebo
treated with active therapies in both phase A and the
for 24 weeks and then switched to metformin 1000mg
continuation phase (range¼32–68% of patients across
b.i.d. for the remaining 30 weeks were included in the
active-treatment groups) were included in this analysis.
safety analysis.
Relative to the CAPT analysis, the completers analysis
showed larger LS mean HbA
1c
changes from baseline for
all groups at week 54 (C01.9% [95% CI: C02.1, C01.8;
Results
n¼124] for high-dose co-administration, C01.7% [C01.8,
C01.5; n¼106] for low-dose co-administration, C01.6%
Ofthe1091patientswhowererandomizedatbaseline,885 [C01.7, C01.4; n¼101] for metformin 1000mg b.i.d.,
(81%) continued into the 30-week continuation phase. A C01.2% [C01.4, C01.1; n¼77] for metformin 500mg b.i.d.,
total of 788 (72%) patients completed all 54 weeks of and C01.4% [C01.6, C01.2; n¼58] for sitagliptin)
treatment, representing similar proportions (65–77%) of (Figure 1B). The proportions of patients in the completers
patients from each treatment group (Table 1). The base- population with an HbA
1c
57% at week 54 were 77%,
line characteristics by treatment group for the randomized 63%, 57%, 35%, and 41% for the high-dose
4
54-week efficacy and safety of sitagliptin/metformin Williams-Herman et al.
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2009 Informa UK Ltd
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